This article is concerned with the persistence and transformations of local authority 'in-house' volunteering programs-which integrate volunteers recruited in a personal capacity in the delivery of local services-during the United Kingdom's 2010-2020 austerity period. Drawing on qualitative research in Newcastle-upon-Tyne's parks, the article highlights a mismatch between volunteers' expectations of what an in-house volunteering program should feel like and what an austerity-shaped one effectively offers them. It centers the concept of 'boundary work' in understanding the mismatch and examining why volunteers remain involved despite it. The article emphasizes boundary work's relational nature, showing how volunteers' continued participation rests not only on their placement of limits but also on their managers' awareness of and commitment to those. It also highlights how managers' dual process of boundary demarcation and boundary downplaying helps to make volunteers' participation feel at times strictly voluntary and at others like a shared endeavor with paid workers- a fluidity which is key to ensuring volunteers' continued involvement in a changing political economic context.
Acceptability is crucial for treatment efficacy, and the World Health Organization emphasizes its impact on patient compliance. Taste plays a significant role in acceptability, with bitter taste often leading to treatment discontinuation. Clozapine, an effective drug for treatment-resistant schizophrenia, faces acceptability challenges that have been connected to its poor taste. The aim of this study was to conduct, for the first time, a human taste assessment of clozapine to directly measure its level of aversiveness. Human volunteer study. Employing a "swirl and spit" method, 23 young healthy adults rated the taste of four clozapine solutions (0.0011-0.018 mg/mL) on a visual analog scale (VAS) ranging from 0 (not aversive) to 100 mm (extremely aversive). Clozapine was not aversive at any concentrations, even at saturation: mean VAS scores ranged from 5.6 to 10.3/100 (median scores ranged between 2 and 4). Reported barriers to compliance linked to taste aversiveness of marketed or extemporaneous dosage forms of clozapine may be linked to factors such as the dosage form itself, other negative formulation or excipients' organoleptic characteristics, packaging, and user instructions linked to dosing frequency and duration, and of course, patient and disease-related factors, which require further investigations. Assessment of clozapine taste in healthy volunteers Clozapine is an antipsychotic used for people who do not respond to other antipsychotics. It is usually taken in tablet form but sometimes patients are given liquid forms of clozapine so that carers can be sure that clozapine has been taken as prescribed. Patients often find the taste of liquid clozapine to be unpleasant, and this aversive taste may make people want to stop taking clozapine. We tested different concentrations of clozapine in volunteers. The taste of clozapine itself was not reported to be unpleasant and most people could taste nothing. We conclude that liquid clozapine has an unpleasant taste because of other chemicals (called excipients) used in making liquid formulations. Clozapine itself appears to be tasteless.
Regulatory agencies request the assessment of the potential of new drugs to cause transporter-mediated drug-drug interactions (DDI). This assessment can be improved by integrating endogenous biomarkers during drug development. Regarding the renal excretion of drugs such as metformin, the organic cation transporter (OCT) 2 and multidrug and toxin extrusion proteins (MATE) 1 and 2-K are of major importance. However, fully validated, sensitive, and specific biomarkers for these transporters are still lacking. In previous in vivo and in vitro studies, 5-aminovaleric acid betaine (5AVAB), serotonin (5HT), and 1-methylhistamine (1MH) emerged as promising biomarker candidates for OCT2/MATE-mediated DDI. Therefore, we further investigated their suitability for clinical risk assessment by evaluating the effects of the OCT2/MATE inhibitor trimethoprim in healthy volunteers and by determining IC50 values for the inhibition of OCT2- and/or MATE1-mediated uptake of the potential biomarkers by trimethoprim, cimetidine, pyrimethamine, and dolutegravir in vitro. Trimethoprim reduced the amount excreted into urine of 5AVAB, 5HT, and 1MH in vivo by 95.1 ± 5.67%, 78.9 ± 6.56%, and 51.9 ± 14.3%, respectively (all P < 0.001) as well as the renal clearance of 5AVAB and 5HT by 93.6 ± 5.85% and 73.8 ± 12.8%, respectively (both P < 0.001). When comparing the IC50 values with unbound inhibitor plasma concentrations, trimethoprim, cimetidine, and pyrimethamine preferentially inhibit the MATE1-mediated transport, whereas dolutegravir inhibits the OCT2-mediated transport of the biomarker candidates. In conclusion, this study further supports the suitability of 5-aminovaleric acid betaine (5AVAB), serotonin (5HT), and 1-methylhistamine (1MH) as promising biomarkers for OCT2/MATE-mediated DDI.
Background Hand grip strength (HGS) is a vital measure of muscular function and serves a pivotal role in the identification of functional impairments, as well as in evaluating the effectiveness of therapeutic interventions in individuals with hand or upper extremity injuries undergoing rehabilitation. HGS represents a simple, objective, and reliable indicator of physical status, muscular performance, cardiovascular fitness, and functional disability. The primary objective of the study was to estimate HGS using a grip force transducer and to establish normative reference data for a healthy population from central India. Secondary exploratory objectives included examining the relationships of HGS with anthropometric and physiological variables, such as age, body mass index (BMI), heart rate (HR), and electromyography (EMG) activity, to provide additional physiological context for interpreting grip strength performance. Methods The study was descriptive and cross-sectional in design and was conducted in the sports physiology laboratory of the Department of Physiology at a rural central Indian medical institute. A total of 400 volunteers aged 17-65 years were selected according to the inclusion criteria. HGS was assessed using a grip force transducer. Surface EMG measurements were obtained through disposable silver-silver chloride electrodes. Data acquisition was performed using the PowerLab system (ADInstruments Pty Ltd., Dunedin, New Zealand), and the analysis was carried out using LabChart Pro software (ADInstruments Pty Ltd., Dunedin, New Zealand). Results Of the 400 participants (220 men and 180 women), the mean age was 34 ± 11 years. The mean HGS was significantly lower in females than in their male counterparts, as revealed by the unpaired t-test. There was also a significant inverse correlation between mean HGS and age in males (r = -0.30) and females (r = -0.36). Although HR was significantly positively correlated with mean HGS, the correlation coefficients were relatively weak (for males, r = 0.23, and for females, r = 0.18), indicating that HR explains only a small proportion of the variability in HGS. The root mean square values of EMG demonstrated a statistically non-significant, weak positive correlation with mean HGS.  Conclusion The present research has established age-specific normative values of HGS, estimated using a grip force transducer, for the healthy population of central India. A statistically significant difference in grip strength was noted between the sexes, with men exhibiting greater grip strength than women. Age and HGS were also found to be inversely related, whereas a statistically significant positive correlation was observed between HR and HGS.
Acute respiratory distress syndrome (ARDS) is characterized by increased alveolar-capillary permeability and neutrophil-driven inflammation. Anumigilimab, a novel, fully human, monoclonal antibody, competitively antagonizes the granulocyte colony-stimulating factor (G-CSF) receptor. This trial aimed to assess its potential in modulating pulmonary inflammation induced by segmental lipopolysaccharide (LPS) challenge. In this randomized, double-blind, placebo-controlled Phase 1b trial (NCT05653713), healthy adults were randomized 1:1 to receive a single intravenous dose of anumigilimab 0.6 mg/kg or placebo (0.9% saline), followed by LPS challenge on Day 3. Biomarkers were measured in bronchoalveolar lavage (BAL) and blood before and after LPS challenge. The primary endpoint was the percentage reduction from baseline in mean absolute neutrophil cell count in BAL following LPS challenge. Secondary endpoints included additional BAL biomarkers of neutrophilic inflammation and tissue injury. Pharmacokinetics, pharmacodynamics, and safety were also assessed. Participants were randomly assigned to anumigilimab (n = 23) or placebo (n = 22). LPS challenge induced expected increases in BAL neutrophils and inflammatory biomarkers, with no significant difference between groups. Target engagement was confirmed by elevated plasma and BAL G-CSF concentrations and transient reductions in peripheral neutrophil counts following anumigilimab administration. Pharmacokinetic/pharmacodynamic parameters were consistent with prior clinical data. Anumigilimab was well tolerated; mild transient neutropenia occurred in four participants treated, with no serious adverse events. While anumigilimab had an acceptable safety profile in healthy volunteers, and favorable pharmacokinetic/pharmacodynamic characteristics, it did not attenuate LPS-induced neutrophilic inflammation. Further preclinical investigations are warranted before advancing its clinical development in ARDS.
Oral flucloxacillin is widely used for methicillin-susceptible Staphylococcus aureus (MSSA) infections, but its recommended 6-hourly dosing may limit adherence. Probenecid inhibits renal tubular secretion of β-lactams and enhances flucloxacillin exposure, allowing less frequent dosing. This study aimed to determine the effect of repeated dosing of probenecid on serum and urinary concentrations of flucloxacillin and its impact on pharmacodynamic target attainment. Ten healthy adults participated. Flucloxacillin was administered intravenously and orally. Oral flucloxacillin was administered with and without probenecid. Rich plasma sampling was undertaken, with analysis by UHPLC-MS/MS. A population PK model was developed and evaluated, followed by Monte Carlo simulations to assess the probability of target attainment (PTA; target of at least 50% fT > MIC at MIC 0.5 mg/L). Urinary biomarkers (NGAL, KIM-1, glycosaminoglycans), urinary flucloxacillin concentrations and serum creatinine concentrations were monitored. Across 307 plasma samples, unbound steady state flucloxacillin concentrations were higher with probenecid (median 0.74 mg/L) than without (median 0.30 mg/L; p = .002). Probenecid reduced flucloxacillin clearance from 143 to 46.9 L/h. Simulations showed markedly improved PTA for flucloxacillin 1 g 8 hourly with probenecid (84%) compared with 1 g 6 hourly alone (6%). Urinary flucloxacillin concentrations were reduced with probenecid, consistent with decreased renal clearance. Serum creatinine concentrations and urinary biomarkers remained stable, and only non-serious adverse events were reported. Co-administration of probenecid significantly enhanced flucloxacillin exposure, without serious adverse effects. These findings warrant evaluation in a clinical trial of patients with MSSA infection. Clinical trial registered with ANZCTR: ACTRN12623001155684.
Nurse counselors play a pivotal role in recruiting and facilitating the retention of volunteers in HIV vaccine trials. They act as the primary interface between the research team and volunteers, typically tasked with educating, supporting, and guiding participants through the trial process, including adherence to the study protocol for care and safety. There is limited research on the series of experiences and challenges faced by nurse counselors during the recruitment and retention of volunteers in HIV vaccine trials. This study aimed to describe the experiences of nurse counselors in recruiting and retaining female sex workers in the HIV PrEP and Vaccine (PrEPVacc) trial. This employed a descriptive qualitative study design nested within the larger phase IIb three-arm, two-stage HIV prophylactic vaccine trial conducted in Dar es Salaam, Tanzania. The qualitative data were collected among three nurse counselors and one field worker who participated in 16 debrief sessions. The participants were purposefully selected due to their roles and responsibilities in the recruitment and retention of volunteers. The audio-recorded sessions were transcribed verbatim, and the content analysis approach was applied. The study revealed that nurse counselors felt responsible and honored through enhancing volunteers' recruitment and enrollment, ensuring retention, and facilitating trial interventions. The availability of a supportive trial environment, engagement meetings, collaboration among staff and volunteers, good staff performance, and volunteers' positive attitude were the qualities for effective management of volunteers in the trial. However, the participants described encountering barriers to trial recruitment and retention, such as volunteers' noncompliance with trial requirements, perceived lack of honesty, personal life and family resistance, stigma, and social perception. The nurse counselors can encounter great turmoil while ensuring recruitment and retention in an HIV vaccine trial. Despite the challenges, volunteer engagement and adherence to study protocol are important for maintaining the continuity of trial procedures over time. Collaboration among staff and engagement of volunteers are essential to enhancing retention until the end of the study. The trial was registered with the US clinicaltrials.gov on 29 September 2021 and can be found at https://clinicaltrials.gov/study/NCT04066881. NCT04066881.
This study investigated the dermatological outcomes of a transferosomal gel encapsulating Niacinamide and Co-enzyme Q10 compared with a conventional base gel in healthy female volunteers over a 12-week period, with a particular focus on key biophysical and aesthetic skin parameters. Before human use, both formulations underwent primary skin irritation testing on rabbit skin, followed by a patch test on healthy volunteers to establish safety. A randomized split-face study design was implemented. Skin hydration, elasticity, melanin, erythema, sebum content, pore size, spots, and wrinkle indices were systematically assessed. Sensory evaluation and appropriate statistical analyses complemented the biophysical measurements. Irritation and patch-test assessments confirmed the nonirritant, well-tolerated nature of both formulations. The transferosomal gel demonstrated significantly higher efficacy (p < .05) across multiple parameters, including hydration, elasticity, melanin, erythema reduction, and sebum regulation. Improvements in pore size, spot reduction, and wrinkle were also more substantial and became evident as early as week 2, with continual enhancement observed throughout the 12-week study. Transferosomal delivery of Niacinamide and Co-enzyme Q10 demonstrates improved topical efficacy compared with conventional formulation, as evidenced by the performance outcomes. It offers a safe, noninvasive delivery strategy for improving skin-related parameters within the study conditions.
The COVID-19 global pandemic persists as an endemic disease with case spikes and a significant continued burden on public health. One hallmark of severe COVID-19 is a dysregulated immune response that leads to systemic inflammation and contributes to disease severity but is not explained by viral replication alone. Severe COVID-19 has been shown to disrupt the gut microbiome and increase intestinal permeability which may contribute to immune dysregulation and systemic inflammation. Here, we investigated the differences in plasma biomarkers for intestinal permeability as well as circulating cytokines between healthy volunteers and patients hospitalized with COVID-19. Correlation analyses were used to characterize differences in biomarker relationships between groups, and a random forest model was used to assess their discriminative accuracy. Our results demonstrated that hospitalized COVID-19 patients have elevated concentrations of pro-inflammatory cytokines and microbial translocation markers, and the relationships between these biomarkers were significantly altered compared to healthy volunteers, especially those related to mucosa-associated homeostatic cytokines IL-17A and IL-23. Further, IL-6 and LBP were the top biomarkers for prediction accuracy in the random forest model. This work highlights the importance of managing microbial translocation in COVID-19 and its potential utility as a biomarker for disease severity.
Rapid globalization and urbanization continue to escalate the burden of non-communicable diseases (NCDs) across the world, disproportionally affecting low- and middle-income countries (LMICs). To date, trials have documented that task-sharing with community health workers (CHWs) can reduce systolic blood pressure (SBP), reduce fasting blood glucose, and achieve smoking cessation. However, most studies have been conducted in rural settings or focused on managing a single condition, such as hypertension only. We propose an open-label, two-armed, community-based cluster-randomized controlled trial in Pokhara Metropolitan City of Nepal, the second largest city in Nepal. A total of 30 clusters will be randomized into intervention or control arm in a 1:1 ratio. An individual is eligible if living in Pokhara Metropolitan City and having one or more of the following conditions: hypertension, type 2 diabetes, and tobacco smoking. The participants will be recruited through study team home visits. The intervention group will receive an intervention package "SCALE-NCD" which includes (1) home-based monitoring, referral, and counseling for self-management of hypertension, diabetes, and tobacco smoking by Female Community Health Volunteers (FCHVs), and (2) weekly mobile phone messages to promote healthy lifestyle. FCHVs are CHWs in Nepal whose usual tasks are limited to maternal and child health care services. The control group will receive usual care, where there is neither of aforementioned two components. Primary outcomes are change in SBP, change in fasting plasma glucose, and change in smoking cessation, the required sample size for which is 405, 105, and 525 per arm, respectively. This study will inform us of the effectiveness of FCHV-led home-based management of the top three NCD risk factors coupled with weekly mobile phone messages in urban Nepal. Building on the previous studies that measured the efficacy of FCHV-led home-based management of a single NCD risk factor in a small geographical area, this scaled-up study will provide us with the realistic impact that FCHVs may have if they are trained to provide primary care services for management of major NCD risk factors. ClinicalTrials.gov NCT06740708. Registered on 2024-12-13.
Photoacoustic tomography is uniquely capable of high-resolution deep-tissue blood-oxygenation (sO2) imaging (oximetry) due to its optical absorption contrast. However, wavelength-dependent optical fluence changes within tissue, i.e., spectral coloring, have impeded the development of photoacoustic oximetry. We present the arterial prior method (APM+; + denotes intravascular fluence correction), which leverages the high arterial sO2 to locally calibrate the optical fluence within tissue to circumvent spectral coloring and reliably estimate the sO2 near the artery. In phantom experiments with ex vivo animal tissue, APM+ resulted in a median estimation error of 2.9% compared to 9.8% from the traditional linear unmixing method (LUM). In human imaging experiments of the radial artery-vein pair in eight healthy adult volunteers, the estimated venous sO2s from APM+ (median: 72.3%, interquartile range/IQR: 8.9%) were concentrated around the typical 60%-80% range in healthy individuals, whereas those from LUM (median: 75.2%, IQR: 34.4%) varied widely. When imaging the wrists of the eight subjects through ex vivo animal tissue of thicknesses up to 1.5 cm, APM+ provided more consistent estimates than LUM, indicating its robustness with depth.
Malaria is responsible for more than half a million deaths each year. Parenteral artesunate is the recommended first-line treatment for severe malaria, but prompt treatment is often delayed affecting patient outcomes. Rectal artesunate is recommended as a pre-referral treatment but shows variable absorption and can be problematic when treating children with gastrointestinal disturbances. Nasal drug administration offers a non-invasive and user-friendly alternative that enables rapid drug absorption. A Phase I, first in human trial was conducted to evaluate the safety, tolerability and pharmacokinetic properties of increasing doses of a novel intranasal formulation of artesunate powder. Three dosing regimens were assessed in adult volunteers. Plasma samples were collected for up to 24 h post-dose for drug measurements of artesunate and dihydroartemisinin. Intranasal artesunate was safe and well tolerated. Only mild adverse events were reported shortly after drug administration. No severe adverse events were observed. Pharmacokinetic analysis confirmed rapid systemic absorption of artesunate but with high inter-individual variability. Dose-normalized exposures to dihydroartemisinin suggested a non-linear dose-exposure relationship. Further evaluation of this novel formulation of artesunate is needed to establish safety and efficacy in patients with malaria. This, first in human, phase 1 provides justification for subsequent phase 2 clinical trials.
To evaluate whether super-resolution deep learning reconstruction (SR-DLR) improves two-dimensional (2D) brain fluid-attenuated inversion recovery (FLAIR) image quality while preserving automated white matter hyperintensity (WMH) volumetry, compared with Gaussian-filtered reconstruction (GA) and denoising DLR (dDLR). Thirty-six healthy volunteers underwent 3T axial 2D FLAIR. Images were reconstructed using GA, dDLR, and SR-DLR (twofold in-plane upscaling). Quantitative metrics (noise, SNR, CNR, sharpness) were measured in standardized regions of interest. Two radiologists independently scored qualitative image quality. In a WMH-positive subgroup, WMH volumes were obtained using a transformer-based U-Net segmentation model on GA, dDLR, SR-DLR, and a high-resolution acquisition (HR-dDLR). Quantitative image-quality metrics were compared using one-way ANOVA, WMH volumes using paired t-tests, and interobserver agreement using weighted kappa. SR-DLR demonstrated the lowest image noise and the highest SNR, CNR, and sharpness compared with GA and dDLR (all p < 0.001). Qualitative scores for noise, sharpness, and overall image quality were significantly higher for SR-DLR (p < 0.001), with perfect inter-observer agreement for sharpness and overall quality. Mean WMH volumes did not differ significantly across reconstructions, and SR-DLR volumes closely matched those of HR-dDLR. SR-DLR substantially improves 2D brain FLAIR image quality at 3T by reducing noise and increasing SNR, CNR, and sharpness while preserving WMH volumetry consistent with high-resolution reference standards.
Dysglycaemia and periodontal inflammation frequently co-occur during pregnancy, but the microbial mechanisms linking these conditions and their potential for intervention remain incompletely understood. Here, we establish prospective pregnancy cohorts including more than 2500 volunteers and longitudinally profile oral microbiome dynamics in 534 pregnant women. We show that gestational diabetes mellitus (GDM) is associated with a progressive shift from Streptococcus-dominated oral microbiota to Prevotella/Porphyromonas-enriched dysbiosis. In mouse and cellular models, this dysbiotic oral microbiota induces periodontal inflammation, systemic IL-17 and IL-1β responses, suppression of glucagon-like peptide-1 and insulin, and exacerbation of hyperglycemia. Conversely, oral microbiota remodeling through transplantation of Streptococcus-dominated bacteria attenuates periodontal inflammation, restores glucagon-like peptide-1 and insulin levels, and improves glycaemic status in mice. Salivary metabolomics identifies docosahexaenoic acid (DHA) depletion in GDM, and in vitro assays show selective suppression of dysbiosis-associated oral pathogens by DHA. We therefore test topical gingival DHA in a double-blind randomized controlled trial of 40 pregnant women with GDM (ChiCTR2400080741), with probing depth and fasting blood glucose as primary endpoints and gingival index, attachment loss and plaque index as secondary endpoints. Daily gingival DHA application for six weeks improves probing depth and attenuates fasting glucose increase compared with placebo, with median fasting glucose changes from baseline of 0.10 versus 0.27 mmol/L. Together, these findings identify oral dysbiosis as a microbial driver of periodontal and glycaemic deterioration during pregnancy and support oral microbiome modulation as a potential adjunctive strategy for pregnancy care, although the clinical findings remain preliminary and require validation in larger trials with broader glycaemic endpoints.
The aim of this study was to evaluate pattern visual evoked potential (PVEP) and pattern electroretinography (PERG) parameters during the attack-free period in patients with multiple sclerosis (MS) with and without a history of optic neuritis (ON), as well as in individuals with non-MS demyelinating diseases and healthy controls. This cross-sectional study included 71 patients with demyelinating diseases (95 eyes) and 44 healthy volunteers (88 eyes). This study was prospectively designed to evaluate clinical and electrophysiological data obtained during the routine diagnostic work-up and follow-up in our Neuro-ophthalmology Unit. Patients were classified into three groups: MS with ON (MS + ON), MS without ON (MS-ON), and non-MS demyelinating disorders with ON (non-MS + ON). All participants underwent a comprehensive ophthalmological examination followed by PVEP and PERG testing. Tests were conducted using the Metrovision Monpack system. The peak latencies and amplitudes of the PVEP N75 and P100 waves, as well as the peak latencies and amplitudes of the PERG P50 and N95 waves, were analyzed and compared with control subjects. To account for inter-eye dependency, we employed Generalized Estimating Equations (GEE), specifying a Gaussian family with an identity link function and an exchangeable working correlation structure. Results are reported as median (range) and Mean Differences (MD) with 95% CI. In the MS + ON group, a significant prolongation of P100 latency along with marked reductions in both P100 and N95 amplitudes was observed (p < 0.001), indicating demyelination accompanied by axonal damage. Additionally, the MS - ON group demonstrated a significant prolongation of P100 latency (p = 0.02) and a reduction in N95 amplitude (p = 0.005), suggestive of subclinical retinal ganglion cell dysfunction in the absence of ON. In the non-MS + ON group, although P100 latency was prolonged (p = 0.01), P100 amplitude was preserved (p = 0.28); however, a significant reduction in N95 amplitude was detected (p = 0.002). Effect sizes were expressed as Mean Differences (MD) with 95% Confidence Intervals (CI) to emphasize clinical magnitude over binary p-values. In combination with PVEP, PERG enhances neuro-ophthalmological evaluation by revealing optic nerve and retinal ganglion cell involvement across both acute and chronic stages of demyelinating diseases.
Although smart insoles have emerged as promising tools for long-term gait analysis, these devices face a trade-off between wearability (where sensor modules are fully accommodated within a compact insole) and data quality (where sensor modules cannot be accommodated within the insole). Integrating an inertial measurement unit (IMU) with pressure sensors and fully embedding all modules may resolve this trade-off; however, the reliability and validity of such a smart insole remain unverified. Can a smart insole with an IMU and pressure sensors provide reliable and valid spatiotemporal gait parameters comparable to an instrumented walkway? Twenty-six healthy volunteers (mean age 26.0 ± 5.6 years) performed walking tasks while wearing the smart insole. Reliability was assessed by comparing spatiotemporal parameters between two sessions of walking trials. Validity was evaluated against a gold-standard instrumented walkway positioned along the path. Data were analyzed using intraclass correlation coefficients (ICCs) and Bland-Altman analysis. ICC values indicated good to excellent reliability (0.93-0.95) and validity against the instrumented walkway (0.70-0.99). Although Bland-Altman analysis revealed systematic differences, these deviations were acceptable (<4% of mean difference), with 95% limits of agreement ratios under 8% for all parameters. The smart insole incorporating IMU and pressure sensors, characterized by a highly wearable and cable-free design, provides reliable and valid spatiotemporal gait parameters. Future studies involving broader populations and real-world settings are warranted to further validate its applicability.
Autoinflation aids assessment of Eustachian tube function, or as a conservative treatment for obstructive Eustachian tube dysfunction. This study compares the physiological characteristics of 2 autoinflation techniques, the Otovent® device and the Valsalva manoeuvre, to inform clinical application for both diagnosis and therapy. Prospective physiological study. Tertiary academic teaching hospital. Twenty-one healthy adult volunteers performed 3 trials of both the Otovent and Valsalva manoeuvres. A linear mixed-effects model (LMM) was used as the primary analysis to compare the mean maximum and plateau nasopharyngeal pressures. Intra-subject repeatability was assessed using the intraclass correlation coefficient (ICC), while inter-subject consistency was evaluated by comparing standard deviations. Eustachian tube (ET) opening rates were measured via tubo-tympano-aerodynamic-graphy, otoscopy, and participant report. The Valsalva manoeuvre generated significantly higher nasopharyngeal pressures. Mean maximum NP pressure for Valsalva (597.5 daPa) was greater than for Otovent (482.3 daPa) (F(1, 104) = 18.82, P < .001). This difference was more pronounced for plateau pressures (Valsalva: 486.0 daPa vs Otovent: 278.0 daPa; F(1, 104) = 126.42, P < .001). Conversely, the Otovent demonstrated markedly superior consistency, showing higher intra-subject repeatability for plateau pressure (ICC = 0.872 vs 0.572) and substantially less intersubject variability (SD ± 39.8 daPa vs ±144 daPa). ET opening rates were comparable between the 2 techniques. Otovent facilitates autoinflation at lower but significantly more consistent pressures than Valsalva. Thus, Otovent may offer greater clinical value when a controlled, repeatable insufflation pressure is required for diagnostic or therapeutic purposes.
Healthcare workers commonly participate in cleft surgery programs to help address global disparities in access to care. The rigor of these programs varies considerably and may not be readily visible to prospective participants prior to engagement. We offer a practical framework to assist prospective volunteers in evaluating cleft surgery programs across domains of patient Safety, Continuity of care, organizational Accountability, Local workforce integration, and Equity and patient rights. The framework is intended for use prior to engagement in overseas clinical work and draws on the authors' combined experience across multiple international cleft surgical programs.
Pistacia lentiscus L. tree is known for its aromatic mastic gum containing terpenes α-pinene and β-myrcene, and has been applied as a traditional remedy in oral care for centuries. Previously, intranasal exposure to mastic resin volatiles increased salivary flow in healthy and dry-mouth individuals. This study assessed the biological effects of oils from P. lentiscus for the purpose of standardisation and optimal performance. Composition analysis (GC-MS/FID) and acetylcholinesterase inhibition of P. lentiscus oils obtained from resin or leaf-twig were assessed in vitro. Salivary properties (flow, spinnbarkeit, total protein concentration) and subjective mouthfeel were analysed before and after the application of the compounds in healthy volunteers (n = 12) in the form of nasal sprays. This study confirmed that both oils tested contain compounds with acetylcholinesterase inhibitory activity in vitro. GC-MS/FID analysis showed different compositions between the resin and leaf-twig oils. Application of leaf-twig oil significantly increased salivary flow (median (IQR), 0.25 (0.15, 0.45) mL/min vs. 0.32 (0.19, 0.51) mL/min, p ≤ 0.01). There were no changes in spinnbarkeit, total protein concentration and mouthfeel. P. lentiscus leaf-twig oil increased salivary flow in healthy participants. Further research is required to assess its effectiveness both in large cohort and in dry mouth patients.
To develop a balanced SSFP (bSSFP) sequence for pulmonary 129Xe dissolved-phase imaging based on a previously described double-echo sequence facilitating separation into red blood cell and membrane signals, to test its feasibility and compare its SNR performance and imaging results to an analogous FLASH sequence. 12 healthy volunteers underwent hyperpolarized 129Xe MRI with both sequences with two different choices of flip angle for FLASH. SNR was quantified using a pseudo multiple replica method, normalized by 129Xe polarization and ventilated volume. Chemical shift separation was performed in k-space taking results from time-domain fits of signal evolution as input, either approximating TE as constant or taking the finite readout duration into account. Results were compared between sequences and methods by linear mixed models, Bland-Altman, and scatter plots. Normalized SNR of the first echo was significantly greater for bSSFP compared to FLASH with the same flip angle, p = 0.003, but not with lower flip angle resulting in equivalent depolarization, p = 0.98. The effective number of signal averages in signal decomposition was significantly higher compared to FLASH with both flip angles and both dissolved resonances, p < 0.008. Neglecting the finite readout duration was found to introduce bias of derived RBC-M ratios but prevent noise amplification. Hyperpolarized 129Xe dissolved-phase imaging using dual-echo bSSFP is feasible and provides superior effective number of signal averages resulting in improved SNR efficiency of signal decomposition. Future work should concentrate on the application in patients with lung disease.